Regulation of Viral RNA Replication

病毒必须以适当的数量和适当的时间产生它们的基因产物。如果不这样做，就会激活宿主的先天防御反应。也许是为了应对来自宿主的挑战，病毒已经适应了许多调节机制，其中许多机制要么协同工作，要么作为分子开关关闭其他过程。 本计画将研究雀麦花叶病毒（BMV）感染模式正链RNA病毒时，调控过程是如何整合的。该项目的三个目标是：1）检查两种竞争结合调节负链RNA合成的病毒RNA基序的细胞蛋白的作用，2）确定BMV衣壳蛋白如何调节从RNA合成到RNA合成的转变，以及3）还表征关键BMV复制蛋白如何在病毒复制酶复合物的翻译和装配中起双重作用。 这项工作的重点代表了一个更综合的方法来研究病毒感染过程的预期结果应该是所有RNA病毒的信息。此外，预期的结果将有助于我们理解基因调控，蛋白质-RNA相互作用和基本过程之间的串扰。 这项研究还将提供一个论坛，培养学生作为问题解决者。 学生将接受培训，使用跨学科的方法来研究病毒病原体。 从高中生到博士后，包括代表性不足的少数民族，有二十多名学生在事先的支持下接受了这个项目的培训。 本研究的下一阶段将继续这一培训传统。

Viruses must produce their gene products in the proper amounts and with the appropriate timing. Failure to do so can activate innate defense responses from the host. Perhaps in response to the challenges from the host, viruses have adapted a number of regulatory mechanisms, many of which work either synergistically or as molecular switches to shut down other processes. This project will study how regulatory processes are integrated during the infection of a model plus-strand RNA virus named Brome Mosaic Virus (BMV). The three objectives of the project will: 1) examine the role of two cellular proteins that compete for binding of the viral RNA motif that regulates minus-strand RNA synthesis, 2) determine how the BMV capsid protein can regulate the transition from RNA synthesis to RNA encapsidation, and 3) characterize also how a key BMV replication protein plays a dual role in translation and the assembly of the viral replication enzyme complex. The focus of this work represents a more integrative approach to studies of the viral infection process the anticipated result should be informative for all RNA viruses. In addition, the anticipated results will contribute to our understanding of gene regulation, protein-RNA interactions, and crosstalk between basic processes. This research will also provide a forum to train students as problem solvers. Students will be trained to use interdisciplinary approaches to study viral pathogens. Over two dozen students, ranging from high schoolers to postdocs, including underrepresented inorities, have been trained on this project with prior support. The next phase of this research will continue this training tradition.